FDA approves prasugrel for prevention of thrombotic CV events during PCI

Daiichi Sankyo and Eli Lilly announced late on Friday that the FDA has approved prasugrel for reducing thrombotic cardiovascular events in patients with acute coronary syndromes who undergo percutaneous coronary intervention.

The approval was based on data from the TRITON-TIMI 38 phase-3 trial, which revealed that treatment with prasugrel (Effient) reduced risk for CV death, myocardial infarction or stroke compared with clopidogrel (Plavix, Sanofi Aventis), according to Elliott Antman, MD, study investigator and professor of medicine at Brigham and Women’s Hospital in Boston.

The trial included 13,608 patients with ACS treated with PCI. Data revealed that 7.0% of patients assigned to prasugrel experienced subsequent nonfatal MI compared with 9.1% of patients assigned to clopidogrel.

Those patients assigned to prasugrel with aspirin had a 19% RR reduction for the combined endpoint of CV death, nonfatal MI or nonfatal stroke compared with clopidogrel and aspirin. This risk reduction was seen as early as three days and continued during the 15 months of the trial. Patients assigned to prasugrel also experienced fewer stent-related clots with an RR reduction of about 50%.

The numbers of deaths and strokes were similar with the two drugs, but patients with a history of stroke were more likely to have another stroke while assigned to prasugrel, according to an FDA press release.

In addition, “prasugrel was associated with a significantly higher risk for serious bleeding events [2.2%] compared with clopidogrel [1.7%]. However, appropriate patient selection may help reduce this risk,” Antman said in the press release.

The risk for bleeding with prasugrel was highest for patients who were either 75, weighed <132 lb or had a history of transient ischemic attacks or stroke.

According to a press release from the companies, prasugrel should be initiated with a loading dose of 60 mg followed by a maintenance dose of 10 mg once daily. For patients who weigh <132 lb, the companies suggested that physicians consider lowering the maintenance dose to 5 mg once daily. Patients assigned to prasugrel should also be assigned to 75 mg to 325 mg aspirin orally once daily, according to their doctors’ instructions.

The drug’s labeling will include a boxed warning alerting physicians of the sometimes fatal bleeding risks with prasugrel, according to an FDA press release.

Prasugrel is contraindicated in patients with active pathological bleeding, a history of transient ischemic attacks or stroke or an urgent need for surgery, including coronary artery bypass. Prasugrel is also not recommended for patients aged 75 or older with the exception of high-risk situations, such as diabetes or a history of MI.

The important breakthrough of this new antiplatelet drug is that its efficacy seems not to be diminished by other commonly used medications. Results of recent studies have demonstrated, for instance, that ubiquitously prescribed proton pump inhibitors abrogate clopidogrel's benefit in coronary artery disease by interference with its metabolism to an active compound. It is unclear whether the slight increase in bleeding and/or stroke development is significant enough not to suggest that prasugrel should virtually always supplant clopidogrel as preferred antiplatelet therapy.

– Harry S. Jacob, MD

HemOnc Today Chief Medical Editor